Blurring the line between ape, man

Ethics

It seems like science fiction: Researchers seeking cures for disease put human cells into the brains of living monkeys, only to worry the animals might become more like people.

But the experiments are real and, according to a paper in the journal Science, the remote possibility of subtle humanlike effects can't be ruled out, even though none has been reported.

As a result, say the scientists, philosophers and bioethicists who wrote the paper, researchers implant-ing human neural stem cells into the brains of primates should follow guidelines designed to discourage the development of monkeys and apes that think or feel more like us.

No one is suggesting that experiments in adult monkeys, such as early tests of treatments for Parkinson's and other diseases, will result in "humanzees" akin to those featured in Robin Cook's novel Chromosome 6. There, monkey-human blends created to produce organs for transplants ended up talking and carrying stone tools.

"We didn't anticipate we'd zap these animals and all of a sudden they're going to turn around and read Rousseau," said Johns Hopkins University bio-ethicist Ruth Faden, one of 22 co-authors of the story in last week's issue of the journal. But, she said, "There's a lot that just isn't known."

Practically speaking, the proposed guidelines are aimed at protecting research animals. Their suffering, for example, might increase if they had more awareness. The guidelines also are aimed at anticipating moral arguments against conducting brain experiments on animals so closely related to humans, potentially resulting in a blurring of the lines between them.

The recommendations -- which include oversight of the experiments and a requirement to monitor and report changes in an animal's cognitive function when possible -- dovetail with those advocated in April by the National Academy of Sciences, an advisory group.

The National Academy's panel, for example, suggested banning the introduction of human embryonic stem cells into a primate in the early stages of the animal's development, something scientists believe is more likely to result in deviations from its normal growth.

Likewise, the authors of last week's article suggested that cognitive and emotional changes are least likely to occur when recipients of neural stem cells are adult members of species more distantly related to humans, such as macaques. Chimpanzees are more closely related.

A number of scientists and medical journal editors have said they expect the research community to largely follow the academy's recommendations. But at least one suggestion made in last week's Science article -- that the proportion of human stem cells injected into adult primate brains be limited -- was greeted with some skepticism.

"That's crazy thinking," said Michael S. Gazzaniga, a member of the President's Council on Bioethics and director of the Center for Cognitive Neuroscience at Dartmouth College. He said the number of cells implanted isn't as important as whether they become part of functioning networks: "How it hooks up intricately is what makes the difference."

And Dr. Evan Snyder, a pediatrician who directs the stem cell program at Burnham Institute in La Jolla, Calif., said it might be important to do some stem-cell testing in young or even prenatal animals to better understand how to combat certain childhood diseases.

Many scientists believe stem cells -- the precursors to all human tissues -- could be a key to fighting health problems from heart disease to Alzheimer's. The Food and Drug Administration generally requires testing in animals, though it doesn't specify what kind, before treatments can be tested in people and, ultimately, approved.

But using stem cells in such testing is controversial, primarily because many are derived from embryos destroyed in the process, something that critics say is an attack on the sanctity of human life.

The group produced its recommendations only after wrestling with fundamental questions about what it means to be human. Members drew on texts in religion, philosophy and law, discussed the muddy scientific differences between nonhuman primates and people, and spoke of what is known -- and the vast amount that is unknown -- about how neural stem cells move about and make connections in the brain once injected.

Funded by the Greenwall Foundation and convened by Hopkins bioethicists, its members included experts from across the country -- and one international member -- on primatology, neuroscience, medicine, bioethics and philosophy.

What stunned some of them was the level of ignorance and disagreement in each of their disciplines on virtually every question addressed.